This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The atomic structure of aquaporin-1 (AQP1) demonstrated how aquaporins are permeated by water but not protons and provided marked insight into several human disorders. Since, not less than eleven mammalian aquaporins have been identified, each with a distinct distribution, and these are selectively permeated by water or water plus glycerol or urea. Nevertheless, regulation aspects are still poorly understood and controversial;pH- or cation-gating theories have been proposed, and there are also evidences that phosphorylation of the cytoplasmic extremities may induce opening of the channel in AQP4.